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BACKGROUND:New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20-69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). METHODS:A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. RESULTS:Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25-69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12-16% and to save 4-13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. CONCLUSION:Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ.